2. Academic Validation
  3. Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia

Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia

  • N Engl J Med. 2010 Dec 2;363(23):2220-7. doi: 10.1056/NEJMoa1002926.
Kiran Musunuru 1,  James P Pirruccello,  Ron Do,  Gina M Peloso,  Candace Guiducci,  Carrie Sougnez,  Kiran V Garimella,  Sheila Fisher,  Justin Abreu,  Andrew J Barry,  Tim Fennell,  Eric Banks,  Lauren Ambrogio,  Kristian Cibulskis,  Andrew Kernytsky,  Elena Gonzalez,  Nicholas Rudzicz,  James C Engert,  Mark A DePristo,  Mark J Daly,  Jonathan C Cohen,  Helen H Hobbs,  David Altshuler,  Gustav Schonfeld,  Stacey B Gabriel,  Pin Yue,  Sekar Kathiresan
Affiliations

Affiliation

  • 1 Cardiovascular Research Center, Massachusetts General Hospital, and Department of Medicine, Boston University School of Public Health, Boston, MA 02114, USA.
PMID: 20942659 DOI: 10.1056/NEJMoa1002926
Abstract

We sequenced all protein-coding regions of the genome (the "exome") in two family members with combined hypolipidemia, marked by extremely low plasma levels of low-density lipoprotein (LDL) Cholesterol, high-density lipoprotein (HDL) Cholesterol, and triglycerides. These two participants were compound heterozygotes for two distinct nonsense mutations in ANGPTL3 (encoding the angiopoietin-like 3 protein). ANGPTL3 has been reported to inhibit lipoprotein Lipase and endothelial Lipase, thereby increasing plasma triglyceride and HDL Cholesterol levels in rodents. Our finding of ANGPTL3 mutations highlights a role for the gene in LDL Cholesterol metabolism in humans and shows the usefulness of exome sequencing for identification of novel genetic causes of inherited disorders. (Funded by the National Human Genome Research Institute and Others.).

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